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Vitamin E mediates cell signaling and regulation of gene expression

Angelo Azzi1, René Gysin, Petra Kempná

  • 1Institute of Biochemistry and Molecular Biology, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland. angelo.azzi@mci.unibe.ch

Annals of the New York Academy of Sciences
|March 9, 2005
PubMed

Insights

Alpha-tocopherol influences cell signaling pathways, affecting cell proliferation and gene expression. This vitamin E form regulates genes involved in tocopherol metabolism, lipid uptake, extracellular proteins, inflammation, and cell cycle, impacting overall cellular function.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cell Biology
  • Nutritional Science

Background:

  • Alpha-tocopherol, a major form of vitamin E, plays a crucial role in cellular processes.
  • Its influence extends to key signal transduction pathways, including protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K).
  • Dysregulation of these pathways is linked to various cellular functions like proliferation, platelet aggregation, and NADPH-oxidase activation.

Purpose of the Study:

  • To elucidate the comprehensive gene regulatory effects of alpha-tocopherol.
  • To identify specific genes and pathways modulated by alpha-tocopherol, independent of or in conjunction with its effects on PKC and PI3K.
  • To understand the mechanisms underlying tocopherol-mediated gene expression changes.

Main Methods:

  • Analysis of gene expression changes in response to alpha-tocopherol treatment.
  • Categorization of regulated genes into functional groups (e.g., tocopherol metabolism, lipid uptake, extracellular proteins, inflammation, cell signaling).
  • Investigation of the involvement of signaling pathways (PKC, PI3K) and transcription factors (NF-kappaB, AP1, PXR/RXR) in tocopherol-induced gene regulation.

Main Results:

  • Alpha-tocopherol modulates gene expression across five distinct functional groups, impacting tocopherol uptake/degradation, lipid metabolism, extracellular matrix, inflammation, and cell cycle regulation.
  • Specific genes like p27, Bcl2, alpha-tocopherol transfer protein, CYP3A, gamma-glutamyl-cysteine synthetase, tropomyosin, IL-2, and CTGF show upregulated transcription.
  • Other genes are downregulated, and regulation is linked to PKC inhibition, transcription factor activity, and potentially PXR/RXR pathways and ARE/TGF-beta-RE elements.

Conclusions:

  • Alpha-tocopherol exerts broad effects on cellular function through intricate gene regulation.
  • These regulatory actions involve modulation of key signaling kinases and transcription factors, influencing diverse biological processes.
  • Understanding these mechanisms provides insights into the physiological roles of vitamin E in health and disease.

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